Harnessing phytoconstituents to treat COVID-19 triggered acute respiratory distress syndrome: Insights from network pharmacology, and molecular modeling

Developing effective therapies for COVID-19-triggered acute respiratory distress syndrome (ARDS) remains a major challenge. Inflammatory signaling molecules have emerged as promising druggable targets. This study employed an integrated network pharmacology and molecular modeling strategy to investigate the anti-inflammatory phytoconstituents (PCs) against COVID-19-triggered ARDS. Putative targets of PCs and disease genes were retrieved from multiple databases, followed by PPI and enrichment analyses, along with network visualization. Network pharmacology identified key phytoconstituents: 1-dehydro-6-gingerol, apigenin-7-glucoside, and quercetin, and crucial targets including EGFR, JAK2, RELA, HSP90AA1, and PIK3CA from the F-B-PCs-T-P network. Enriched inflammatory pathways included Toll-like receptor, PI3K-Akt, NOD-like receptor, and HIF-1 signaling. Molecular docking and dynamics simulations further confirmed stable, high-affinity interactions between these targets and selected PCs. Specifically, apigenin-7-glucoside showed strong binding with JAK2 and RELA, while quercetin favoured JAK2 and EGFR. Overall, the findings underscore the therapeutic potential of these PCs and validate integrated in silico approaches (in) drug discovery. A strategy to identify potential phytoconstituents and targets for treating COVID-19-triggered ARDS. ● Network pharmacology identified EGFR, JAK2, RELA, HSP90AA1, and PIK3CA as crucial targets in COVID-19 triggered ARDS. ● Apigenin-7-glucoside showed strong binding affinity with JAK2 (–10.0 kcal/mol) and RELA (–8.0 kcal/mol). ● Quercetin exhibited favourable interactions with JAK2 (–9.3 kcal/mol) and EGFR (–8.5 kcal/mol). ● Repurposing apigenin-7-glucoside and quercetin as potential therapeutic candidates for COVID-19 triggered ARDS.